Menthol Regulation for Smoking Cessation

Overseen By Tracy T Smith

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical University of South Carolina

Disqualifiers: Other tobacco, Pharmacotherapy, Health, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 7 weeks

240 Participants Needed

Trial Summary

What is the purpose of this trial?

In a 2x2 design, current menthol smokers (N=240) will complete a baseline period before being assigned to a cigarette (menthol or non-menthol) and e-cigarette condition (menthol or tobacco-flavored e-liquid) and receiving a 7-week supply of cigarettes and e-cigarettes. The study builds upon our well-established methodology for simulating tobacco regulatory policies. To model a ban, smokers will be instructed to only use their assigned products. Primary outcomes include cigarette smoking and e-cigarette use during Week 6. However, because a menthol ban may impact the ability to abstain from smoking, the investigators will incentivize participants to abstain from smoking during Week 7 (continued e-cigarette use allowed) and assess the time to first lapse. Participants will complete daily electronic diaries assessing tobacco product use throughout, which will be corroborated by biomarkers for menthol, nicotine, and smoke. Finally, to maximize the utility of these data for FDA regulation, the investigators will assess whether any demographic or baseline smoking characteristics moderate the observed treatment effects, calibrate the treatment effects to the US adult menthol smoking population, and model the effects of menthol regulation in cigarettes and e-cigarettes on smoking and vaping-attributable deaths and life-years lost.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of menthol regulation as a treatment for smoking cessation?

Research indicates that the method of menthol delivery in cigarettes does not significantly impact smoking cessation, nicotine dependence, or quit attempts. Additionally, menthol is a biologically active compound, but its effects on smoking cessation are not well established. ^{1 2 3 4 5}

Is menthol safe for use in smoking cessation treatments?

Menthol in cigarettes and e-liquids is a biologically active compound that can affect health, but studies show mixed results on its safety compared to non-menthol products. While menthol reduces the harshness of smoke, making it easier to start smoking, its overall health impact is still not fully understood, and conclusions about its safety are inconclusive. ^{4 5 6 7 8}

How is the treatment of menthol regulation for smoking cessation different from other treatments?

This treatment is unique because it focuses on regulating menthol in cigarettes and e-cigarettes, which could lead to a significant number of menthol smokers quitting if menthol products are banned. Unlike traditional cessation programs, this approach targets the availability of menthol flavors, which are a key factor in smoking initiation and maintenance. ^{5 8 9 10 11}

Eligibility Criteria

This trial is for adults over 21 who regularly smoke menthol cigarettes, use a specific brand most often, and have been smoking at least 5 cigarettes daily for one year. Participants must own a smartphone capable of receiving texts and internet access to complete diaries.

Inclusion Criteria

You need to have a smartphone that can receive text messages and access the internet so you can complete a diary.

You typically use mentholated products.

I have been smoking 5 or more cigarettes daily for at least a year.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline

Participants complete a baseline period before being assigned to a cigarette and e-cigarette condition

1 week

Treatment

Participants receive a 7-week supply of cigarettes and e-cigarettes and are instructed to only use their assigned products

7 weeks

Weekly electronic diary entries

Practice Quit Attempt

Participants are incentivized to abstain from smoking during Week 7, with continued e-cigarette use allowed

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Menthol Cigarettes
• Menthol Flavored E-cigarettes
• Non-Menthol Cigarettes
• Tobacco Flavored E-cigarettes

Trial Overview The study tests the impact of using non-menthol cigarettes vs. menthol ones, alongside menthol or tobacco-flavored e-cigarettes in a simulated regulatory environment. Over seven weeks, smokers' cigarette and e-cigarette usage patterns are monitored with incentives to abstain from smoking in the final week.

Participant Groups

Group I: Non-menthol Spectrum Cigarettes and Tobacco E-cigarettes Experimental Treatment 2 Interventions

Ppts will be randomly assigned to receive the non-menthol spectrum cigarettes and Njoy Ace tobacco e-cigarettes. Will be used for the duration of the study (8 weeks) starting at the second visit.

Group II: Non-menthol Spectrum Cigarettes and Menthol E-cigarettes Experimental Treatment 2 Interventions

Ppts will be randomly assigned to receive the non-menthol spectrum cigarettes and Njoy Ace menthol e-cigarettes. Will be used for the duration of the study (8 weeks) starting at the second visit.

Group III: Menthol Spectrum Cigarettes and Tobacco E-cigarettes Experimental Treatment 2 Interventions

Ppts will be randomly assigned to receive the menthol spectrum cigarettes and Njoy Ace tobacco e-cigarettes. Will be used for the duration of the study (8 weeks) starting at the second visit.

Group IV: Menthol Spectrum Cigarettes and Menthol E-cigarettes Experimental Treatment 2 Interventions

Ppts will be randomly assigned to receive the menthol spectrum cigarettes and Njoy Ace menthol e-cigarettes. Will be used for the duration of the study (8 weeks) starting at the second visit.

Menthol Cigarettes is already approved in European Union, United States, Canada, Brazil for the following indications:

Approved in European Union as Menthol Cigarettes for:

• Not approved due to ban on menthol cigarettes

Approved in United States as Menthol Cigarettes for:

• Not approved due to proposed ban on menthol cigarettes

Approved in Canada as Menthol Cigarettes for:

• Not approved due to ban on menthol cigarettes

Approved in Brazil as Menthol Cigarettes for:

• Not approved due to ban on menthol cigarettes

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

University of Minnesota

Collaborator

Trials

1,459

Recruited

1,623,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

Menthol smokers using JUUL were more likely to switch from cigarettes to vaping compared to nonmenthol smokers, with 42.6% of menthol smokers switching versus 38.8% of nonmenthol smokers, indicating a potential advantage of ENDS for this group.

A significant preference for Menthol/Mint-flavored JUULpods was observed among menthol smokers (53.8%) compared to nonmenthol smokers (22.9%), suggesting that offering menthol-flavored ENDS could enhance switching rates among menthol smokers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences in switching away from cigarettes and JUUL use characteristics among adult menthol and nonmenthol smokers who purchased the JUUL System. Goldenson, NI., Augustson, EM., Shiffman, S.[2022]

Inhaled menthol from e-cigarettes did not enhance the positive effects of nicotine but significantly increased negative effects in non-menthol-preferring smokers and reduced smoking urges in menthol-preferring smokers.

Menthol-preferring smokers experienced blunted positive responses to nicotine and less severe withdrawal symptoms, potentially due to slower nicotine metabolism linked to chronic menthol exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute effects of inhaled menthol on the rewarding effects of intravenous nicotine in smokers. Valentine, GW., DeVito, EE., Jatlow, PI., et al.[2020]

About 40% of US smokers use mentholated cigarettes, with most preferring those mentholated in the tobacco itself, but the method of menthol delivery did not affect their ability to quit smoking or their level of nicotine dependence.

In a study analyzing data from the Population Assessment of Tobacco and Health, it was found that only 12% of smokers quit between the first and second waves of the study, indicating that cessation rates were not influenced by whether the menthol was in the tobacco, in a filter capsule, or not present at all.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Menthol Cigarettes and Smoking Cessation among Adult Smokers in the US. Schneller, LM., Bansal-Travers, M., Mahoney, MC., et al.[2021]

Menthol in cigarettes is a biologically active compound that may influence health effects, but the specific impacts compared to non-menthol cigarettes are not well understood due to limited research.

The review highlights that while menthol affects various health aspects such as toxicity, lung function, and inflammation, many findings are inconclusive, making it difficult to draw definitive conclusions about its overall health effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The health effects of menthol cigarettes as compared to non-menthol cigarettes. Hoffman, AC.[2021]

A study of 38 vape shop websites in the Greater Los Angeles Area identified 1330 e-liquid flavors, with 219 categorized as menthol, mint, or ice flavors, indicating a significant presence of cooling flavors in the market.

The majority of these cooling flavors (70.3% of ice flavors and 63.3% of menthol flavors) were marketed in combination with fruit, suggesting a trend towards appealing flavor profiles that may attract a wide range of consumers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A content analysis of website marketing for cooling flavored e-liquids in a sample of brick-and-mortar vape shops in the Greater Los Angeles area. Brown, N., Shin, H., Whooley, S., et al.[2022]

Studies comparing menthol and nonmenthol cigarettes have shown inconsistent results regarding their toxicity, leading manufacturers to claim that menthol does not increase harm.

The authors argue that focusing solely on toxicity is too limited and does not adequately address the broader public health concerns associated with menthol cigarettes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Menthol should not be given a free pass based on studies of biomarkers of toxicity. Clark, PI., Gardiner, P.[2018]

Menthol cigarettes are particularly popular among younger smokers, with 56.7% of 12-17 year olds and 45.0% of 18-25 year olds using them, compared to lower rates in older age groups.

While overall smoking rates for non-menthol cigarettes decreased among adolescents and young adults from 2004 to 2010, menthol cigarette use remained constant or even increased, indicating that mentholated cigarettes may hinder efforts to reduce youth smoking rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential trends in cigarette smoking in the USA: is menthol slowing progress? Giovino, GA., Villanti, AC., Mowery, PD., et al.[2022]

In a study of 64 black and Latinx menthol cigarette smokers, both menthol and non-menthol e-cigarettes showed similar high rates of switching and acceptability, indicating that restricting menthol e-liquids may not negatively impact these smokers' transition to e-cigarettes.

Participants using menthol e-cigarettes reported comparable reductions in daily cigarette consumption and similar subjective effects to those using non-menthol e-cigarettes, suggesting that both types of e-cigarettes are effective alternatives for menthol smokers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Menthol versus non-menthol flavouring and switching to e-cigarettes in black and Latinx adult menthol combustible cigarette smokers: secondary analyses from a randomised clinical trial. Nollen, NL., Leavens, ELS., Ahluwalia, JS., et al.[2023]

Among 6257 participants seeking help from quitlines, 18.7% were menthol smokers, who were generally younger, more likely to be female, and had lower education levels compared to nonmenthol smokers.

Cessation outcomes for menthol smokers who enrolled in quitline services were similar to those of nonmenthol smokers, indicating that quitlines are effectively serving both groups, but a potential ban on menthol cigarettes may increase demand for these services.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cessation outcomes among treatment-seeking menthol and nonmenthol smokers. D'Silva, J., Boyle, RG., Lien, R., et al.[2022]

Flavored tobacco products are particularly popular among youth and young adults, with 80% of youth and 73% of young adults currently using them, highlighting their appeal as starter products for tobacco use.

The study found that having a flavored product as a first tobacco experience is linked to a significantly higher likelihood of continued tobacco use, with a 13% increase in youth and a 32% increase in adults who started with flavored products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Flavored Tobacco Product Use in Youth and Adults: Findings From the First Wave of the PATH Study (2013-2014). Villanti, AC., Johnson, AL., Ambrose, BK., et al.[2022]

In a study of 267 young adult smokers, those who started with menthol cigarettes were significantly more likely to continue using them after one year, indicating that menthol may play a strong role in smoking initiation and persistence.

While menthol smokers expressed a greater intention to quit smoking, they were less likely to take immediate action to quit compared to non-menthol smokers, suggesting that menthol may influence not just smoking habits but also cessation behaviors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns of Longitudinal Transitions in Menthol Use Among US Young Adult Smokers. Rath, JM., Villanti, AC., Williams, VF., et al.[2018]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Differences in switching away from cigarettes and JUUL use characteristics among adult menthol and nonmenthol smokers who purchased the JUUL System. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Acute effects of inhaled menthol on the rewarding effects of intravenous nicotine in smokers. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Menthol Cigarettes and Smoking Cessation among Adult Smokers in the US. [2021]

4. Greece pubmed.ncbi.nlm.nih.gov

The health effects of menthol cigarettes as compared to non-menthol cigarettes. [2021]

5. Greece pubmed.ncbi.nlm.nih.gov

A content analysis of website marketing for cooling flavored e-liquids in a sample of brick-and-mortar vape shops in the Greater Los Angeles area. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Menthol should not be given a free pass based on studies of biomarkers of toxicity. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Differential trends in cigarette smoking in the USA: is menthol slowing progress? [2022]

8. England pubmed.ncbi.nlm.nih.gov

Menthol versus non-menthol flavouring and switching to e-cigarettes in black and Latinx adult menthol combustible cigarette smokers: secondary analyses from a randomised clinical trial. [2023]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Cessation outcomes among treatment-seeking menthol and nonmenthol smokers. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Flavored Tobacco Product Use in Youth and Adults: Findings From the First Wave of the PATH Study (2013-2014). [2022]

11. England pubmed.ncbi.nlm.nih.gov

Patterns of Longitudinal Transitions in Menthol Use Among US Young Adult Smokers. [2018]